JP4691445B2 - Patch injection device - Google Patents

Description

  The present invention relates generally to substance delivery devices, and more particularly to patch-like, wearable, self-contained substance injection devices that can be used to deliver various substances or medications to a patient.

  Many people need periodic delivery of drugs or other compounds to maintain health. For example, people with diabetes use daily insulin infusions to maintain tight control of blood glucose levels. Currently, there are two main methods of daily insulin therapy in the case of insulin infusion therapy. The first method includes a syringe and an insulin pen. These devices are easy to use and relatively inexpensive, but typically require a needle stick every 3 to 4 injections per day. The second method is infusion pump therapy. The therapy involves the purchase of expensive pumps that last about 3 years. The initial cost of the pump is a high barrier for this type of therapy. However, from the user's point of view, the vast majority of patients using pumps want to continue using the pumps in the future. This provides the advantage of continuous infusion of insulin, accurate dosing and programmable delivery schedules, although infusion pumps are more complex than syringes and pens. This leads to more precise blood sugar level management and improved health promotion awareness.

  As their interest in intensive therapy increases, users typically turn to insulin pumps. However, in addition to their high cost (about 8-10 times the daily cost of injection therapy) and limited lifetime, insulin pumps represent a relatively old technology and are difficult to use. Also, from a lifestyle perspective, tubing (known as an “infusion set”) that connects the pump to the delivery side of the user's abdominal cavity is very inconvenient and the pump is relatively heavy and carries the pump It is troublesome to do.

  However, patients who regularly use oral agents eventually move to insulin, and existing pump therapies are very expensive. There is a growing interest in better therapies, revealing previously confirmed progress in pump therapies and increased number of daily injections. In such and similar infusion cases, what is needed to fully satisfy this increased interest is that the best features of daily injection therapy (low cost and ease of use) It is a form of insulin delivery or infusion that combines with the features of (continuous infusion and precise dosing) and avoids the respective disadvantages.

  Several attempts have been made to provide a walkable or “wearable” drug infusion device that is low in cost and convenient to use. Some of these devices are intended to be partially or wholly disposable. In theory, this type of device can provide the many advantages of an infusion pump without the associated costs and inconveniences. Unfortunately, however, many of these devices are uncomfortable for the user (depending on the needle gauge and / or length of the needle used), compatibility and materials used to construct the delivered material and infusion device. Disadvantages, including interaction with the device, can be disadvantageous and may not start properly if not properly activated by the user (eg, a “soaked” injection resulting from premature activation of the device). In particular, when short and / or fine gauge needles are used, difficulties in manufacturing and adjusting the needle penetration depth have also been encountered. It can also cause needlestick injury to those who come into contact with the device used.

  Thus, there is a need for alternatives to current infusion devices such as insulin infusion pumps. The requirement is to further provide ease of use for manufacture and regular delivery of drugs and other compositions to patients.

  It is an object of the present invention to provide a patch injection device that is conveniently applied to the skin and can provide injection of a desired substance.

  It is another object of the present invention to provide a patch injection device that provides a patient needle or needles that are hidden prior to and during use, unlike conventional syringes.

  It is another object of the present invention to provide a patch injection device that minimizes discomfort by using one or more microneedles.

  Another object of the present invention is to provide a patch injection device that can be secured to a patient via an adhesive surface.

  Another object of the present invention is to provide a patch injection device that provides a container for pressurizing the contents.

  It is another object of the present invention to provide a patch injection device that provides a container for pressurizing the contents using a bladder and disc spring assembly.

It is another object of the present invention to provide a patch injection device that allows pressurization of the contents of a container through a single or any secondary energy application step.
Another object of the present invention is to add the contents of the container in a single or any secondary energy application step by removing the disc spring that holds the pin through a pull handle assembly. It is an object of the present invention to provide a patch-like injection device that allows pressure to be applied.

  It is another object of the present invention to provide a patch injection device that provides for the implantation of a patient's needle and delivery of the contents of a container via a single or any secondary activation step.

  Another object of the present invention is to provide a patch injection device that can be activated via a moderate force applied to a vertical or horizontal push button in a single or any secondary activation step.

  Another object of the present invention is a patch injection device that allows pressurization of container contents, implantation of a patient's needle and delivery of container contents through a combined single energy application and activation step. Is to provide.

  Another object of the present invention is to provide a patch injection device that allows visual inspection of the contents of the device before, during and after use.

  Another object of the present invention is to provide a patch injection device that automatically shields or covers a patient's needle or needles when intentionally or accidentally removed from the skin surface.

  Another object of the present invention is to provide a patch injection device that provides an interlock between the puller member assembly and the push button to prevent accidental activation.

  Another object of the present invention is to provide a patch injection device that allows removal of a patient's needle cap and / or puller member assembly and / or adhesive cover in one or more movements. is there.

  Another object of the present invention is to provide a patch injection device that facilitates self-injection and reduces or eliminates variations in injection technology between users.

  One or more that may be placed in liquid communication with a container assembly that includes a rigid bladder portion that is used in conjunction with a bladder film, such as a metallized film, which is generally non-inflatable during normal use. These or other objectives are generally achieved by providing a patched, wearable, self-contained substance injection device system and method that provides a generally hidden patient needle. Simple removal of the retaining pin allows the disc spring or disc spring assembly to apply an essentially uniform and constant pressure to the contents of the container assembly, and then the device is skinned through the adhesive contact surface. Allow to be attached to the surface. Next, one or more spring-loaded patient needles are released and seated within the skin surface to establish a fluid communication path between the patient needle and the contents of the pressurized container. , Thereby providing a push button activation assembly used to deliver the infusion of contents into the user's skin.

  Various objects, advantages and novel features of preferred embodiments of the present invention will be readily understood from the following detailed description taken in conjunction with the accompanying drawings. It will be understood that throughout the drawings, like reference numerals indicate like parts, components or configurations.

(Introduction)
Embodiments of the device described below provide a convenient patch for delivering a pre-measured dose of a substance such as a drug or drug to a user via an infusion device attached with an adhesive. It can be used as a device. The device is self-contained and is attached to the user's skin surface with an adhesive disposed on the bottom surface. Once properly positioned and activated by the user, the pressure of the released disc spring on the container surface within the device causes the flexible container to pass through one or more patient microneedles via the needle manifold. Can be used to empty the contents. The substance in the container is then delivered through the user's skin by a microneedle that is driven into the skin by one or more springs included in the device. It will be appreciated that alternative embodiments are possible in which the disc spring is replaced with a different type of energy storage device that may be mechanical, electrical and / or chemical in nature.

  As will be appreciated by those skilled in the art, there are numerous ways to implement the patched syringe or infuser system disclosed herein. Although reference is made to the embodiments depicted in the drawings and the following description, the embodiments disclosed herein exclude various alternative designs and embodiments encompassed by the disclosed invention. Does not mean. In each of the disclosed embodiments, the device is referred to as an injector. However, the device can also inject substances at a much faster bolus rate than is normally achieved with an injector device. For example, the contents can be delivered in a short period of a few seconds or a long period of a few days.

(General structure)
In a first embodiment according to the present invention shown in FIGS. 1 to 11, the injection device 1000 includes a container subassembly 100. The container subassembly 100 includes an upper housing 110, a container base surface 120, at least one disc spring 130, a holding pin 140, a filling plug 150, a partition wall 160 and a container film 170. The infusion device 1000 further includes a housing subassembly 200. The housing subassembly 200 includes a lower housing 210 and a patient needle manifold 220 having at least one patient needle 222 and a manifold film 224. The housing subassembly 200 further includes a needle shield 230, a needle shield drive spring 232 and an adjustable needle cap 240. The adhesive layer 250 is disposed on the lower surface of the lower housing 210 and is covered by a removable film (not shown) and a pull handle 260. A clip 270, such as an “E” shaped clip, can be used to secure the retention pin 140 to the puller member 260. The infusion device 1000 further includes a push button subassembly 300. The push button subassembly 300 includes at least one patient needle manifold drive spring 310, push button feed base 320, at least one septum needle 330, septum needle shield 340, and fluid communication tube 350. Yes. A button front surface 360 may be provided to complete the push button subassembly 300. In the following description, the term container is often used to describe the assembled container subassembly 100 and the individual container base surface 120, fill plug 150, septum 160 and container film 170 of the container assembly 100.

As mentioned above, the components of the embodiment shown in FIGS. 10A-10C are grouped into several subassemblies as presented below for ease of description. Such subassemblies include, but are not limited to, a container subassembly 100, a housing subassembly 200, and a push button subassembly 300. An assembled embodiment of the present invention is shown in FIGS. The cross-sectional view illustrative are shown in Figures 6-9.

  As shown in FIGS. 1-5, an embodiment of the present invention 1000 is a patch-like, wearable, self-contained that is comprised of these subassemblies and can be used to deliver a variety of drugs to a patient. A substance injection device may be provided. The device 1000 showing the pre-energization and pre-activation state in FIG. 1 includes a hidden patient needle or needles before and during use and can be firmly secured to the patient via an adhesive surface. . Pressurization of the contents of the container can be accomplished by removing the puller member 260 and can “energize” the device and the device contents. The device can then be “activated” via an appropriate force applied to the push button 360 to seat the patient needle and establish a flow path between the container and the needle. In so doing, the device 1000 facilitates self-injection and reduces or eliminates variations in injection technology between patients.

  FIG. 1 is a top perspective view of a first embodiment of an injection device 1000. In FIG. 1, the assembled upper housing 110 and lower housing 210 are shown. Between these housings is a push button subassembly 300. The puller member 260, described in detail below, is shown in a pre-energized and pre-actuated position to help secure the retaining pin 140 in the device and shield the push button 360 from the applied force. Yes. As more clearly shown in FIG. 2, which is a bottom perspective view of the first embodiment, the puller member 260 is further coupled to the holding pin 140 via a needle cap 240 and a clip 270. Further, as illustrated in FIG. 6 which is a cross-sectional view (6-6 in FIG. 1) of the first embodiment, the pulling member 260 is further coupled to the push button feed base 320. The top view of the first embodiment shown in FIG. 3 illustrates the arrangement between the pushbutton feed base 320 and the device and the amount of movement required for activation. 4 is a side view of the first embodiment, illustrating the centering of the opening of the patient needle clearly illustrated by the inconspicuous portion of the device and the bottom view of the first embodiment shown in FIG. Yes.

  FIGS. 6 to 9 and FIGS. 11A to 11C illustrate a number of cross-sectional views of the first embodiment (6-6 in FIG. 1), in a position before energization and before activation, followed by energization. 6 illustrates the structure, positioning and operation of each subassembly in the post-start position. Each is described in more detail in the following sections.

(Container subassembly)
FIG. 10A shows a container subassembly 100 of an infusion device 1000 that is used in conjunction with a non-expandable but flexible film 170 such as one or more metallized films. It may be composed of a rigid portion 120. The container assembly 100 can contain any number of materials between both the first film and the second fill. Either the first film or the second film is also disposed relative to the hard portion, or is disposed between the first film and the hard portion.

  The rigid portion 120 or container base is comprised of the rigid portion of the container to which the flexible film 170 can be pressed and functions as the rigid portion of the container, as will be described in detail below. As more clearly shown in FIG. 6, the rigid portion 120 has a recessed central area 122 and allows the flexible film 170 or film lid to be heat sealed to the rigid portion and the contents therebetween. And a flange 124 provided around the outer periphery of the rigid portion to form a container or chamber. The container subassembly of FIG. 10A mates with a guide 126 for accurately positioning and mounting between the rigid portion 120 and the upper housing 110 using any number of techniques such as ultrasonic staking. A guide opening 112 that may be received may be further provided.

As described above, the container of the embodiment shown in FIG. 10A preferably has a hard shell or inner surface and at least one flexible film attached around the periphery of the hard shell or inner surface. Can be configured as follows. The flexible film 170 is heat sealed to the rigid portion 120, creating a chamber or bladder for storage of the contents of the device. Since at least one wall of the chamber is made of a flexible film 170 and at least one wall of the chamber is made of a hard surface, one or more disc springs 130 are arranged in the vicinity of the flexible film 170. It can be used to apply a substantially constant pressure to the flexible film 170 to pressurize the chamber and contents of the container.
6 and 10A, the disc spring 130 is provided to apply a substantially uniform and constant pressure to the flexible film 170 of the container subassembly 100, so that the flexible film 170 and the rigid portion 120 The contents of the container in between are compressed and the contents are forced from the container through one or more fluid passages as shown in detail in FIG. FIG. 12 illustrates a partial cross-sectional view of the fluid passageway and the container subassembly of FIG. 10A. As described above, the container of FIG. 10A may also be made of two or more flexible, non-inflatable films. In this case, the contents can be sandwiched between films where at least one film is attached to the rigid portion 120 to provide a rigid base that compresses and pressurizes the contents of the container. In yet another embodiment of the container subassembly 100, the flow rate is automatically adjusted from an initial high flow rate to a low flow rate that is reduced by one or more steps. Further details regarding flow regulation are discussed in US patent application Ser. No. 10 / 396,719, filed Mar. 26, 2003, entitled “Multistage Fluid Delivery Device and Method”. The entire contents of which are hereby incorporated by reference.

  The flexible film 170 of the container subassembly 100 can be made from a non-intumescent material or a laminate such as a metallized film or other similar substance. For example, one highly flexible flexible laminated film that can be used in the container subassembly 100 of the first embodiment is selected based on the first polyethylene layer, barrier properties, and provides an attachment mechanism for the third metal layer. It may be composed of a second chemical layer known to those skilled in the art, followed by a fourth layer of either polyester or nylon. By utilizing a metallized or metallized film 170 in conjunction with the rigid portion 120, the barrier properties of the container are improved, thereby increasing the shelf life of the contents contained therein, That is, improve. For example, if the container contents include insulin, the primary material of the contact portion within the container subassembly 100 of the embodiment described above is linear low density polyethylene (LLDPE), low density polyethylene (LDPE), cyclic olefin Contains copolymer (COC) and Teflon. As will be described in detail below, the primary materials of the contact portion in the remaining flow path of the contents of the container include polyethylene (PE), medical acrylic resin and stainless steel. Such materials that are in extensive contact with the contents of the container subassembly preferably pass ISO 10-993 and other suitable biocompatibility tests.

  The containers of the container subassembly 100 can be stored in an appropriate controlled environment for a defined storage period of the contents of the container without adversely affecting the contents, and are applicable to various environmental conditions. More preferably, it is possible. Furthermore, the barrier provided by the container components does not allow the transfer of or to the contents of gases, liquids and solid materials at a faster pace than allowed to achieve the desired shelf life. In the embodiment shown in FIG. 10A, the material of the container subassembly can be stored and manipulated in a temperature range of about 34-120 degrees Fahrenheit (1-49 ° C.) and can be 2 years or longer. May have years of storage. For example, as shown in FIG. 13, the container subassembly described above has no effect on insulin stability during use with the device. 13 is a graph illustrating an example of insulin stability data for the container subassembly of FIG. 10A.

  In FIG. 13, the stability of the insulin in the container contents plotted as insulin concentration values along the Y axis is shown over a 25 day (or more days) shelf life for six insulin containing devices. ing. The device to be compared includes a first embodiment according to the present invention having a 4 cc container, a 25 cc container, and a 37 cc container in addition to the 4 cc, 25 cc, and 37 cc glass bottle insulin storage devices. As shown in FIG. 13, the insulin concentration of the stability test sample hardly changes over 25 days. Also, there is little or no difference between plots for each device over the same period. In addition to meeting stability requirements, the container can further ensure operation by passing many leak tests that hold the sample without leakage for 20 minutes under 30 psi (about 207 kPa) pressure. . Additional filling, storage and delivery benefits due to the configuration of the container subassembly include minimal space and flexibility within the sealed container, as will be described in more detail below.

  The containers of container subassembly 100 are preferably emptied prior to filling, as will be described in detail below. By emptying the container of FIG. 10A prior to filling and having only a slight recess 122 in the hard floor of the hard portion 120, the sealed space and excessive waste within the container can be minimized. Further, the shape of the container can be configured to fit the type of energy application mechanism used, for example, a disc spring or a disc spring having dimensions such as any number of diameters and heights. In addition, using a emptied flexible container during filling minimizes air and air bubbles in the filled container. The use of a flexible container is also very advantageous when the device is affected by external pressure or temperature changes that cause the internal pressure of the container to increase. In such a case, the flexible container expands and contracts with the contents, thereby preventing the possibility of leakage due to the expansion and contraction forces applied to the filling plug 150 and the septum 160. This also helps to eliminate dose changes due to temperature and pressure fluctuations in the surrounding environment.

  As described above, the small recess 122 provided on the surface of the rigid portion 120 helps to prevent the formation of a fluid retaining pocket when the container film 170 collapses under the pressure of the disc spring 130. This indent also helps to fill the container system by providing a fluid flow path since it is preferable to empty the system prior to introducing fluid into the system. Such introduction of fluid can be accomplished completely when the device is manufactured or by the end user's use. For example, in one filling method, the container may be emptied, filled via the fill port 152 and subsequently capped with a fill plug 150. Alternatively, in the second filling method, the container may be emptied and subsequently capped with a filling plug 150 and then filled through the filling plug 150 before use. This allows the container of the device to be received in the drug filling position in such a way as to allow aseptic filling with a small sealed space and a sterile maintenance connection of the fluid flow path. As described in detail below, any container access needle and patient needle can be capped in a sterile maintenance manner.

  Yet another feature of the container subassembly 100 includes the ability to allow automatic particle inspection by the user during filling or use. One or more container obstructions, such as the rigid portion 120, can be molded from a clear, clear plastic material that allows inspection of the material contained in the container. The transparent and clear plastic material is preferably a cyclic olefin copolymer characterized by high transparency and clarity, solubility and low biocompatibility with the material contained in the container. In such applications, the container is associated with minimal properties that can interfere with inspection (ie, rotation while inspection is allowed).

(Flow path)
The rigid portion 120 of the container subassembly 100 of FIG. 10A further comprises at least one flow path 128 as shown in FIG. 12 that reaches the main chamber 127 of the container. In the embodiment shown in FIG. 12, the flow path 128 exits the container's main chamber 127 and is a heat seal area provided around the outer periphery of the rigid portion 120 to secure the flexible film 170. Passes down or through it and enters the chamber 129 between the fill head plug 150 and the septum 160, allowing the container fluid to be transported from the container to the septum 160. In the embodiment shown in FIG. 12, the flow path 128 is preferably configured to reduce dead volume and includes a fill head receiving shape as described in detail below.

  The flow path 128 is constructed of a material that is similar or identical to the material described above with respect to the container subassembly and that satisfies a number of biocompatibility and storage tests. For example, as shown in Table 1 below, when the contents of the device include insulin, the primary materials of the contact portion within the container subassembly 100 of the embodiment are linear low density polyethylene, cyclic olefin copolymer and It contains Teflon and may contain clear and clear plastic. The primary material of the contact portion in the remaining flow path between the container subassembly and the microneedle 222 of the patient needle manifold 220 includes polyethylene, medical acrylic resin and / or stainless steel.

  In particular, the patient needle 222 and septum needle 330 are each made from stainless steel, the septum needle manifold 322 and the patient needle manifold 220 are made from polyethylene and / or medical acrylic resin, and the septum 160 is a halo. The septum needle and / or the flexible tube 350 between the septum needle manifold and the patient needle manifold is made from polyethylene with a PVC outer layer and an ethyl vinyl acetate bonding layer. Such materials preferably pass the ISO 10-993 biocompatibility test when in extensive contact with the contents of the container subassembly.

  The septum 160 of FIG. 10A is disposed between the first fluid passage 128 and the second fluid passage comprising the septum needle 330, the septum needle manifold 322, and the tube 350, and is separated by the septum nail or the septum needle 330. When pierced, it may be an elastomeric plug that creates a sterile flow path between the container and the patient needle 222. The partition needle 330 used to penetrate the partition wall 160 and create a flow path between the first fluid path and the second fluid path is a partition needle before and after the boot is crushed and the fluid path is created. A septum needle boot 340 that maintains the sterility of

  As will be described in more detail below, septum needle 330 is significantly larger than, for example, a 25-29 gauge patient needle 222, allowing for easy handling and prevention of flow restrictions. As more clearly shown in FIGS. 10C and 12, the septum needle boot 340, or sheath, is large enough to engage a recessed opening 342 provided in the septum elastomer plug 160 before being pierced by the septum needle 330. It is made. This engagement between the septum needle boot 340 and the recessed opening 342 provided in the septum elastomer plug 160 causes the septum needle 330 to move through the septum needle boot and septum. Because it creates a sterile environment, there is no time for the septum needle to be exposed to a non-sterile environment.

(Head port for filling)
Returning to FIGS. 10A and 12, the chamber 129 between the septum 160 and the container is also accessed via a filling head port 152 located in the container subassembly 100 that can be closed with a filling head plug 150. Can be done. The filling head plug 150 and the partition wall 160 may be the same part. This reduces manufacturing complexity.

  Through the use of the fill head port 152, the device can be allowed to fill containers from an external source after assembly is complete and / or even in use. In the first filling method, the completed and fully assembled device is provided in place of the filling head port 152 without the filling plug 150, and then the filling plug or filling head plug is filled. It can be added after filling the container with the device. Alternatively, in the second filling method, a completed and fully assembled but not yet filled device is provided with a filling head plug 150 in place in the filling head port 152, and then A standard syringe or similar device can be used to fill by injection through the filling head plug. Since the top of the container can be made from a transparent material, the degree of filling and excess air can easily be seen and can be withdrawn using the same syringe. In this way, careful control of fill and dose delivery is maintained.

  For prefilled infusion devices, the fill head port 152 includes a fill head plug 150 that closes the fill head port. At this time, the upper housing 110 can be used to hold the filling head plug 150 in place, prevent the plug from coming off, and access the filling head plug to fill the desired location. Can provide. For an infusion device that allows filling in use, the filling head port 152 passes through the inner collar beyond the filling head plug 150 that passes through or is removed from the filling head plug 150 as described above. Either is accessible. In each filling application, the filling head port 152 allows fluid to be transferred from an external source to the main chamber 127 of the container subassembly 100 via the fluid path 128 described above. The main chamber 127 further includes an input port and an output port useful for filling.

  If the filling in use is to take place, the device does not require the activation steps outlined below. When the device is to be filled in use, the disc spring 130 is retracted by the retaining pin 140 because the pressure exerted on the empty container by the released disc spring has no effect. Does not need to be held in position. Filling the device in use is the displacement of the disc spring 130, which can freely push the container subassembly and force the contents out of the container once the external filling pressure source is removed from communication with the container. To help. Furthermore, such filling in use allows aseptic packaging steps without the limitations imposed by the device containing the drug.

(Disc spring)
As shown in FIG. 10A, a disc spring or disc spring 130 is included in the device 1000 to apply an essentially uniform and constant force to the container and force the contents out of the container. The spring 130 is hereinafter sometimes referred to as a “a constant force spring”. Constant force spring 130 is used to store energy that pressurizes the container in use when released upon activation of the device. The spring 130 is held in a bent state by a pin 140 positioned at the center of the plurality of spring fingers. In doing so, the spring is prevented from stressing the film 170 of the container subassembly 100 or any of the remaining device components during storage.

  Pin 140 or retention pin is a suitable pin, tube or ring that is stiff enough to prevent tension and displacement of the spring and secure the pin to a removal mechanism such as the puller member 260 described in detail below. obtain. The pin 140 will not fail under normal tensile loads, or if it is part of an assembly, it will be disassembled with a force that can be triggered during shipping and handling, resulting in accidental activation. I don't have to.

  In FIG. 10B, the puller member 260 is provided to aid in the removal of the retention pin 140 described above. The puller member 260 is disposed near the bottom surface of the device and includes one or more members extending to one side of the device, creating a mechanical advantage for removal of the retaining pin 140. In the embodiment shown in FIG. 10B, the puller member 260 includes a member 262 that protrudes and shields the button head 360 of the push button subassembly 300. By doing so, the puller member 260 prevents a force from being applied to the push button 360 until the puller member is removed. This prevents accidental activation of the device via a push button before normal installation.

  In the embodiment described above, the puller member 260 includes a member that prevents force from being applied to the push button. In another form of this embodiment, the puller member may include a member that extends between the push button and the device housing and prevents movement of the push button when a force is applied to the push button. Good.

  Further, another puller member / push button interlock mechanism may be provided between the puller member 260, the needle cap 240, and the holding pin 140. This interlocking mechanism ensures normal operation and prevents accidental activation. For example, in FIG. 10B, the puller member 260 also protrudes from the surface of the puller member into the opening of the pushbutton feed base 320 until the puller member is removed and the device is activated until the pushbutton 360 is activated. A member 264 that prevents the application of the force from moving the carriage.

  In yet another form of the embodiment described above, the push button and button platform itself may serve to release the retaining pin. In this case, when the push button is activated, the holding pin is inclined from a position substantially perpendicular to the disc spring. As the retaining pin is increasingly tilted, it is eventually released from the disc spring. Removal of the puller member 260 also includes a tactile and audible indicator that provides feedback to the user.

  When the retaining pin 140 is released from the disc spring 130 and withdrawn, the spring finger retracts, thereby applying a force to the film lid 170 of the container subassembly 100. The edge of the spring 130 is confined between the container and the upper housing and is preferably about 1 to 50 psi (about 6.9 to 345 kPa), more preferably about 2 to about, for intradermal delivery of the contents of the container. It may be configured to create a pressure in the vessel of 25 psi (about 13.8 to about 172 kPa), most preferably about 15 to about 20 psi (about 103 to about 138 kPa). For subcutaneous injection or injection, a range of about 2-5 psi (about 13.8-34 kPa) is sufficient.

  The disc spring has a diameter of between about 1.15 to 1.50 inches (about 2.9 to 3.8 cm), preferably 1.26 inches (3.2 cm) to allow delivery of up to 600 μl. Can have. As shown in FIG. 14, a commonly found disk spring calculation graph known to those skilled in the art is used to calculate the optimal spring shape. As shown in FIG. 14, a number of charts show the load deflection characteristics for dish washers with different height-thickness ratios. As is known to those skilled in the art, a washer or disc spring exhibits a load characteristic expressed as a load deflection in a horizontal position when the spring transitions from a horizontal or bent state to a relaxed state. As shown in FIG. 14, the selection of a spring having a specific height-thickness ratio can be used to create a desired load deflection profile.

(Housing sub-assembly)
Returning to FIG. 10B, the bottom or lower housing 210 is provided so that it can mate with the upper housing 110 and the container subassembly 100 described above. The lower housing 210 is used to contain and contain all remaining components and may provide a snap function for receiving and mounting components and housing members. The lower housing 210 also includes one or more guiding features to secure, release, and guide the button carriage 320 and patient needle manifold 220, as described in more detail below. obtain. A break line between the units, for example between the upper housing unit and the lower housing unit, can be arranged towards the vertical center line of the device. The device creates a firmer assembly because the push button subassembly described below can be loaded upside down in a sturdy housing instead of on a flat plate. The upper housing 110 and the lower housing 210 may be snap-coupled or ultrasonically coupled to each other.

  Upper housing 110 and lower housing 210 each further allow for the use of separate subassembly elements. In that case, each component can be built-in and is stable. For example, the assembled and separated containers, particularly the container base surface 120, the filling plug 150, the septum 160, and the container film 170 of the container assembly 100, do not include any extra parts, resulting in a low filling operation. Bring a load. Furthermore, all stored energy elements can be accommodated separately from the container. So these elements cannot be inadvertently deployed during filling.

(Microneedle)
Returning to FIGS. 10B and 10C, the disclosed device also includes at least one patient needle 222 or microneedle, but the three microscopic devices shown, for example, in the push button subassembly 300 of FIG. 10C. Several needles may be included like a needle. Each microneedle 222 is preferably at least 31 gauge or smaller, such as 34 gauge. Each microneedle 222 is also secured within a patient needle manifold 220 that may be placed in fluid communication with the container. Each microneedle is secured to prevent disassembly from the manifold 220 with a force of 1 pound (about 4.4 N) or less. The microneedle 222 may also have a different length or gauge, or a combination of different lengths and gauges if more than one needle is included in the device. The microneedle 222 includes one or more ports along the length of the main body, preferably near the tip of the needle or, if the needle has, the tip bevel. Also good.
In the embodiment described above, a plurality of 34 gauge needles for delivering the container contents as the infusion occurs over a longer period typically associated with a quick syringe injection requiring a very large cannula or needle. The use of is practical. In the disclosed embodiment, any microneedle can be used as long as it targets either intradermal or subcutaneous space. However, the embodiment shown in FIG. 10C includes a microneedle having an exposed length of between 1 and 4 mm (ie, 2 mm) and includes any number of needles as required by a particular application. Also good.

(Push button subassembly)
FIG. 10C shows a push button sub-assembly 300 that integrates septum needle 330, septum needle manifold 322, and push button feed base 320. However, the configuration of the push button subassembly 300 may be somewhat simplified by providing a snap-on push button faceplate 360 to allow for two or more simple molded button parts. The pushbutton platform 320 also provides a mechanism to lock the patient needle manifold in the retracted position and release the manifold when the device is properly activated.

  As shown in FIG. 10C, the tube 350 used to establish the fluid path as described in more detail below allows for easy assembly and is provided between the septum needle manifold and the patient needle manifold. A flexible fluid path is created and exits septum needle manifold 322 on the same side as the inlet of the tube to patient needle manifold 220. The patient needle manifold 220 containing the patient needle 222 is incorporated into tracks 324 provided on the button platform 320, as described in detail below, to provide a stable locking and release mechanism. produce.

  As shown in FIG. 10C, a pair of detents 326 and 328 may be provided along the track 324 to hold the button platform 320 in place at various stages or curved surfaces. For example, the button subassembly 300 of FIG. 10C provides a number of positions to allow for container loading, patient needle and septum needle manifold assembly, housing welding, and user activation. . Specifically, at least three positions are provided.

  The first or assembly position is provided for container loading and housing welding. Because the patient needle manifold 220 is held against movement with respect to the slidable movement of the button carriage 320, the first position is that the groove 221 of the patient needle manifold 320 is the first of the button carriage 320. Provided to engage a set of detents 326. In this position, loading can occur without interference between the bulkhead boot 340 and the bulkhead 160.

  The second or transport position is provided for shipping and establishes a seal between the septum needle boot 340 and the septum 160. Since the patient needle manifold 220 remains stationary with respect to the slidable movement of the button carriage 320, the second position is provided such that the button carriage is slidably engaged, The groove 221 of the needle manifold remains in the track 324 and is disengaged from the first set of detents 326 and subsequently engages the second set of detents 328 of the button feed base 320. In this position, the septum needle boot 340 engages the recessed opening 342 provided by the septum elastomer plug 160 before being pierced by the septum needle 330. This engagement between the septum needle boot and the recessed opening creates an aseptic environment through which the septum needle moves as it pierces both the septum needle boot and the septum. Therefore, there is no time for the septum needle 330 to be exposed to a non-sterile environment. This effectively eliminates the effects of minor remote field welding.

The third position is provided as an activated or in-use position. Since the patient needle manifold 220 remains stationary with respect to the slidable movement of the button carriage 320, the third position is provided such that the button carriage is slidably engaged, The needle manifold groove 221 is disengaged from the second set of detents 328 and remains in the track 324 until it aligns with the track opening 325 and then becomes free and free from the button platform 320. Become. In this third position, the septum 160 is pierced and the manifold and safety mechanism, both described in detail below, are released and driven by the spring 310 to force it toward the user's skin surface. Pushed down. In the embodiment shown, the force required to pierce the septum 160, press the septum needle boot 340, release the patient needle manifold 220 and move it to this third position is typically 2-4 pounds (about 8.9-17.8 N).

  Patient needle manifold assembly 220 and septum needle manifold assembly 322 allow access and release of fluid contained in the container and delivery of fluid to patient needle 222, respectively. Each manifold housing thus routes the contents of the container received from the septum needle 330 or other protuberance and associated tube 350, directing the contents toward the patient needle 222 and the user. It contains a number of fluid flow paths for delivery into the skin. The patient needle manifold 220 to which the patient needle 222 is fixed is in fluid communication with the septum needle manifold 322 to which the septum needle 330 is fixed by a flexible tube 350.

  Patient needle manifold 220 is held in a pre-release or “up” state by push button subassembly 300 and lower housing 210 under the load provided by one or more springs 310. In the first version of fixing the patient needle manifold 220 in the ready state described above, the patient needle manifold 220 is slidably engaged with a set of tracks 324 disposed on the button feed base 320. Yes. Since the patient needle manifold 220 remains stationary within the achute 212 provided by the lower housing 210, the button carriage 320 slides until the track opening 325 is aligned with the patient needle manifold 220. Move movably to release the patient needle manifold 220 from the track 324 within the spigot.

  In the second version of securing the patient needle manifold 220 in a ready state, one or more protruding blocks (not shown) extend from the button feed base 320 to connect the needle manifold 220 to one or more. Hold the ready state under the load provided by the spring 310. During activation, the button platform 320 is slidably moved, guided along the path of movement by the functions of the lower housing 210 and the button platform 320, and released toward the user's skin surface for movement. The block is moved freely from the needle manifold 220. As the block moves freely from the patient needle manifold 220, the manifold falls and the needle 222 sits on the user's skin. Further details of the support block are further mentioned in the above referenced US patent application 60 / 420,233. The entire contents of which are hereby incorporated by reference.

  In each of the versions described above, when activated or released from the ready state, one or more springs 310 apply a force to the top of the patient needle manifold 220 to drive the manifold, When released, allows the patient needle 222 to sit and creates a fluid path between the septum needle, septum needle manifold, flexible tube, patient needle manifold, and a series of patient needles. The drive spring 310 “places the needle on the skin via a spring-loaded patient needle manifold 220 that can move at speeds in the range between 15-26 miles / hour (6-12 m / sec). plant) ”.

  The slidable movement of the button feed base 320 also pushes the septum needle 330 via the septum needle boot 340 and the septum 160, creating a flow path between the container and the septum needle. The manifold 322 containing the septum needle is mounted or configured as a component of the button carriage 320 and moves with the button carriage during the activation step until the septum needle 330 penetrates the septum boot 340 and subsequently the septum 160. . Depending on the desired sequence, before, simultaneously with, or slightly after the septum needle 330 penetrates the septum 160, the patient needle manifold 220 is released and falls to the skin surface, causing the patient needle 222 to be seated and thereby the container. Through the septum needle and the septum needle manifold, through the flexible tube attached to the septum needle manifold, and to start the flow of energized fluid to the patient needle of the patient needle manifold.

  One or more septum needles 330 may be provided separate from the patient microneedles 222, allowing a large flow in the completed fluid path between the container and the patient needle. In the embodiment described above, the completed fluid path partially includes two or more needles, specifically, at least one septum needle 330 and at least one patient microneedle 222. This allows the device to incorporate differently structured needles depending on the desired fluid path characteristics. For example, the patient microneedle 222 may include one or more 34 gauge needles. In this case, septum needle 330 may include one or more required or the same or larger needles. Furthermore, the separation of the patient needle and the septum needle further allows freedom of movement of the patient needle during operation of the device.

  Flexible tube 350 may be used to connect septum needle 330 and / or septum needle manifold 322 to patient needle manifold 220. The flexibility of the connecting tube allows the patient needle manifold 220 to be moved more independently from the rest of the device and allows the needle to sit more effectively. Once properly seated, the patient needle manifold 220 completes the fluid path between the flexible tube 350 and the series of patient microneedles 222 and the user's skin. As mentioned above, the patient needle manifold 220 is guided into place by the configuration of the lower housing 210. The drive spring 310 described above then applies a force to the top of the patient needle manifold 220, taking into account seating of the needle when the manifold is released. There are various drive spring options, including the use of only one or as many as four coil springs or one or more leaf springs.

  A detailed embodiment of the patient needle manifold 220 is shown in FIGS. 15A and 15B. FIG. 15A is a perspective view of a preferred embodiment of a patient contact surface shape of a patient needle manifold for a patient needle manifold 220, and FIG. 15B is a perspective view of another patient contact surface shape. Further details of the manifold are provided by the same applicant, such as Alex Lastvich, whose title is “Apparatus and Method for Delivering or Withdrawing Substances Through the Skin” filed on Feb. 4, 2003. No. 10 / 357,502, the entire contents of which are hereby incorporated by reference. Further details of the manifold are also disclosed in U.S. Patent Nos. 60 / 447,359, 60 / 450,680 and 60 / 450,681, referenced above, the entire contents of each. Are also incorporated herein by reference.

  In the patient needle manifold embodiment shown in FIGS. 10C and 15, at least one fluid communication path or feed channel is provided for each patient needle 222. The manifold may simply have a single flow path for one or more patient needles, or there may be a number of fluid paths or paths that route the contents separately for each needle. It may be provided. These channels or paths may further comprise a tortuous channel for the moving contents, thereby affecting the fluid pressure and delivery rate and acting as a flow restrictor. The path or flow path within the patient needle manifold 220 may vary in width, depth and shape depending on the application. Here, the width of the path is typically between 0.015 and 0.04 inch (about 0.04 to 0.1 cm), preferably 0.02 inch (about 0.05 cm) and the manifold Is configured to minimize dead space within. As further shown in FIG. 10C, the patient needle manifold 220 also includes a film lid 224 made of the material outlined in Table 1 to seal the manifold and the exposed manifold path. . Similar to the fluid path analysis described above and outlined in Table 1, the material of the film lid 224 is also selected to be fully compatible with the contents of the device, and a minimum that will leave few particulates. Provide an extract of In yet another embodiment of a patient needle manifold, the manifold may be sealed without a film such that the manifold includes a pathway confined within the manifold body.

  The skin contact surface of the patient needle manifold 220 shown in FIG. 15A shows a skin contact surface having a plurality of exposed needles, each needle protruding from a needle cone 226. Each needle cone 226 includes or is located near one or more adhesive reservoirs 228 that are provided to allow coupling between the patient needle 222 and the patient needle manifold 220. obtain. As illustrated in FIG. 15A, each of the patient needle cones 226 is preferably non-uniform around the entire cone circumference, with the removed portions of the needle cone having varying sizes and depths. May be included. Such a section or cut-out portion of the patient needle cone 226 is removed to create an adhesive reservoir 228 or provide a laser welding access path, required with minimal penetration into the manifold flow path. Each needle can be secured within the needle cone at a height.

  Another version of the skin contact surface of the patient needle manifold 220 is shown in FIG. 15B (only the contact surface is shown). The needle cone of FIG. 15B includes cone portions removed both above and below the patient contacting surface that are arranged as described with respect to the version of FIG. 15A. However, in the version shown in FIG. 15B, a tapered recess is also provided extending below the removed portion of the patient needle cone adjacent to the needle opening. Thus, as shown in FIG. 15A, the removed portion may simply be a removed section around the cone above the patient contact surface, or it may be more extensive as shown in FIG. 15B. Larger sections around the cone that extend further into the manifold surface to provide an adhesive reservoir may be removed.

  The removed portion and adjacent indentation described above can be used to assist in front bonding the patient needle 222 into the patient needle manifold 220 during manufacture, and other types of fixation such as laser welding. Can be easy. Such a front face bonding method allows a reduction in the height of the chamber within the manifold where the smooth end of the needle 222 is located, and further prevents the adhesive from depositing in and around the fluid path within the manifold. To do. Undesirable introduction of adhesive into these fluid pathways can create unknown or indeterminate dead volume within the patient needle manifold 220 itself, as well as create adhesive / drug interaction problems. is there. The use of front side bonding provides a higher rate of repeatability that allows for the exact calculation of dead volume due to adhesive, which is just present. However, the placement of such adhesive on the patient contact surface shown in FIGS. 15A and 15B prevents glue glues around the base of the needle, which can reduce the length of the exposed needle. It is preferable to be monitored carefully.

  The embodiments of the subassemblies presented above are not limiting and can be modified in structure to meet the requirements of a given application. For example, another embodiment of the subassembly described above is shown in FIGS. FIG. 16A is a top perspective view of another embodiment of the subassembly of FIGS. 10A-10C, partially assembled. 16B and 16C are cross-sectional views of the subassembly shown in FIG. 16A before and after energy application and activation, respectively. As shown in FIG. 16A, the lower housing 180 may be configured to slidably receive an integral push button platform 182 having a septum needle 184 similar to the button platform assembly 320 described above. A wider patient needle manifold 186 with at least one patient needle (not shown) may also be included. The manifold extends parallel to the movement of the button carriage and includes first and second drive springs 188. In the subassembly embodiment shown in FIG. 16A, septum needle 184 and patient needle manifold remain in fluid communication substantially through flexible tube 190 as described above, FIG. As shown, the patient needle manifold is allowed to move unconstrained once released.

The engagement of the button platform assembly 182 within the lower housing 180 of the embodiment shown in FIGS. 16A-16C provides an overall lower device shape in addition to improving handling and manufacturing requirements. The flexible tube 190 is more easily adapted to the embodiment and allows for a simplified push button platform.

(operation)
The devices described above are suitable for use in administering various substances, including drugs and pharmaceuticals, to patients, particularly human patients. As used herein, pharmaceutical agents include biologically active substances that can be delivered through body membranes and body surfaces, particularly skin. Examples listed in more detail below include antibiotics, antiviral agents, analgesics, anesthetics, appetite suppressants, arthritis treatments, antidepressants, antihistamines, anti-inflammatory agents, antitumor agents, DNA vaccines Includes vaccines. Other substances that can be delivered to the patient intradermally or subcutaneously include human growth hormone, insulin, protein, peptides and fragments thereof. Proteins and peptides exist in nature and can be chemically synthesized or recombinantly produced. Furthermore, the device can be used in cell therapy methods such as during intradermal injection of dendritic cells.

Still other substances that can be delivered in accordance with the present invention are drugs, vaccines, etc. that are used to prevent, diagnose, ameliorate or recover from illnesses using drugs. The agents include alpha-1 (Alpha-1) antitrypsin, antitumor-induced angiogenic agents, antisense, butorphanol, calcitonin and analogs thereof, Ceredase® , COX-II inhibitors, Dermatological drugs, dihydroergotamine, dopamine agonists and antagonists, enkephalins and other opiate-like peptides, epidermal growth factor, erythropoiesis stimulating factor and the like, follicle stimulating hormone, granular colony stimulating factor, glucagon, granular Macrophage colony-stimulating factor, granisetron, growth hormone and the like (including growth hormone releasing hormone), growth hormone antagonist, hirudin agonists such as hirudin and hirulog, immunoglobulin E inhibitory gene, insulin, insulinotropin and the like Analogue, insulin-like growth Factor, interferon, interleukin, luteinizing hormone, luteinizing hormone-releasing hormone and the like, low molecular heparin, macrophage colony stimulating factor, metoclopramide, midazolam, monoclonal antibody, anesthetic analgesic, nicotine, nonsteroidal anti-inflammatory Sex agents, oligosaccharides, ondansetron, parathyroid hormone and the like, parathyroid hormone antagonists, prostaglandin antagonists, prostaglandins, recombinant soluble receptors, scopolamine, serotonin agonists and antagonists thereof, Contains sildenafil, terbutaline, thrombolytics, human tissue plasminogen activator, tumor necrosis factor and tumor necrosis factor antagonist, vaccines with addiction, arthritis, cholera, cocaine addiction with or without carriers / adjuvants ,diphtheria, Wound, Haemophilus influenza b type bacteria, Lyme disease, meningococcus, measles, mumps, rubella, chickenpox, yellow fever, respiratory syncytial virus, tick-borne Japanese encephalitis, pneumococcus, streptococci, typhoid fever , Hepatitis including influenza, hepatitis A, B, C and E, otitis media, rabies, polio, human immunodeficiency virus, parainfluenza virus, rotavirus, Epstein-Barr virus, cytomegalovirus, clazimia, non-capsular hemophilus , Moraxella catarrhalis, human papilloma virus, Mycobacterium tuberculosis including BCG, gonorrhea, asthma, atherosclerosis, malaria, Escherichia coli, Alzheimer's disease, Helicobacter pylori, Salmonella, diabetes, cancer, herpes simplex, human papilloma Preventive drugs and curative antigens (proteins, And polysaccharides, polysaccharide conjugates, toxoids, genetic-based vaccines, live, attenuated, genetically hybrid, inactive whole cells, viral and bacterial vectors) And other similar substances include, for example, cold medicine, anti-addiction, anti-allergy, antiemetics, anti-obesity, anti-osteoporosis, anti-infectives, analgesics, anesthetics, anorexia, Anti-arthritis drugs, anti-asthma drugs, anti-migraine preparation drugs, motion sickness prevention preparation drugs, antiemetic drugs, anti-neoplastic drugs, anti-Parkinson syndrome drugs, anti-itch, antipsychotic drugs, antipyretic drugs, anticholinergic drugs, benzodiazepine antagonists Medicine, whole body, heart, peripheral and cerebrum, bone stimulant, central nervous stimulant, hormone, hypnotic, immunosuppressant, muscle relaxant, parasympathomimetic, parasympathomimetic, prostaglandin, protein, peptide, Polype Important treatments such as vasodilators, psychostimulants, sedatives, hyposexuality and tranquilizers, including peptide and other macromolecules, and, for example, tuberculin and all its contents are incorporated herein by reference Important diagnostic methods, such as other hypersensitivity drugs as described in US Pat. No. 6,569,143, whose title is “Method of Injecting Intradermal Substance” Includes all of

  Vaccine formulations that can be delivered according to the present invention can be selected from the group consisting of antigens or antigenic components capable of eliciting an immune response against human pathogens. The antigen or antigenic component may be a type 1 human immunodeficiency virus (such as the protein tetanus antitoxin, nef, gp120 or gp160), gD or its inducer, or an early protein such as ICP27 from HSV1 or HSV2 ( Human herpesvirus (HSV) such as Immediate Early protein), cytomegalovirus (such as gB or its inducer) (CMV (especially human)), rotavirus (including live attenuated virus), gp350 or Epstein-Barr virus (such as its inducer), varicella-zoster virus (VZV such as gp1, type II and IE63), or hepatitis B virus (eg, hepatitis B surface antigen or derivative thereof), A Hepatitis viruses (HAV), hepatitis viruses such as hepatitis C virus and hepatitis E virus, Are other viral pathogens such as paramyxovirus, respiratory syncytial virus (RSV like F protein or G protein or their inducer), parainfluenza virus, measles virus, mumps Cold virus, human papilloma virus (eg HPV like HPV6, 11, 16, 18), flavivirus (eg yellow fever virus, dengue virus, tick encephalitis virus, Japanese encephalitis virus) or influenza virus (egg or MDCK) A whole or attenuated virus grown in a cell, a partially split influenza virus, or a whole influenza virosome or a product or recombinant protein thereof, HA, NA or M protein or their Or something like a combination) Or Neisseria spp, including Neisseria gonorrhoeae and Neisseria meningitidis (eg, capsular polysaccharide and its conjugates, transferrin binding protein, lactoferrin binding protein, PilC protein (PilC), adhesins); group A Hemolytic streptococci (eg, M protein or fragments thereof, C5A protease, lipoteichoic acid), group B streptococci, mutans streptococci; flexible gonococci; cataract (eg, high and low molecular weight) Moraxella spp including M. catarrhalis, also known as adhesin protein and invasins); Bordetella pertussis (eg, pertactin, pertussis toxin and its derivatives, filamentous Hemagglutinin, adenylate cyclase, fluff (fimbriae), parapertussis, bronchial sepsis Bordetella spp, including mycobacteria; tuberculosis mycobacteria (eg, ESAT6, antigen 85A, 85B or 85C), bovine tuberculosis, lei, tuberculosis, M. paratuberculosis, Mycobacterium spp, including S. pneumoniae; Legionella, including Legionella pneumophila; entrotoxic E. coli (eg, colonization factors, thermolabile toxins or derivatives thereof , Heat-stable toxins or derivatives thereof), enterohemorrhagic E. coli, enteropathogenic E. coli (eg, Shiga toxin-like toxin or derivatives thereof); Escherichia spp; cholera (eg, these toxins or derivatives thereof) Vibrio spp, Shigella spp, Shiga Shigella, Shigella spp including group B Shigella; Enterocolitica (eg Y opprotein), Yersinia genus including Plasmodium pestis and pseudotuberculosis; Campylobacter spp including Campylobacter jejuni (eg, toxins, adhesin protein and invidin) and Campylobacter spp; Salmonella typhi, Paratyphi Salmonella spp, including Vibrio cholerae, Enterococcus; Listeria spp, including Listeria; Helicobacter spp, including H. pylori (eg, urease, catalase, cell vacuolating lethal toxin); Pseudomonas spp containing bacteria; Staphylococcus spp containing Staphylococcus epidermidis, Staphylococcus spp Enterococcus spp containing staphylococci, Enterococcus spp; Derivatives thereof), Clostridium botulinum (for example, botulinum toxin and so ), Clostridium spp, including C. difficile (eg, Cristoridium toxin A or B, and derivatives thereof); Bacillus spp, including carbon bacteria (eg, Clostridial toxin, and derivatives thereof) Corynebacterium spp containing diphtheria (eg, diphtheria toxin and derivatives thereof); Borrelia burgdorferi (eg, OspA, OspC, DbpA, DbpB), Borrelia gallini (eg, OspA, OspC) , DbpA, DbpB), Borrelia afzeli (eg, OspA, OspC, DbpA, DbpB), B.I. B. andersonii (eg OspA, OspC, DbpA, DbpB), Borrelia spp, including B. hermsii; Ehrlichia spp, including agents for E. coli and human granulocyte ehrlichiosis; Rickettsia spp, including spotted fever rickettsia; Chlamydia spp, including Chlamydia (eg Chlamydia major outer membrane protein, heparin binding protein), pneumonia chlamydia (eg Parrot disease Chlamydia, heparin binding protein); parasitic bacteria (Leptospira spp) Syphilis treponema (eg, a bacterial outer membrane protein), Treponema denticola, T .; Parasites derived from Treponema spp including T. hyodysenteriae or including Plasmodium spp .; Toxoplasma (eg, SAG2, SAG3, Tg34) ) Toxoplasma spp; Entamoeba spp including dysentery amoeba; Babesia spp including B.microti; Trypanosoma spp including Trypanosoma cruzi; Giardia spp including Rumble flagellate; Leshmania spp including Leishmania P. genus Pneumocystis spp with Carini pneumonia; Trichomonas spp with Trichomonas vaginalis; Schizostoma ssp with Schistosoma mansoni; or Candida with Candida albicans Yeast bacteria such as the genus (Candida spp); the title of the invention is published as “vaccine delivery system” in the international publication of WO 02/083214, and the contents thereof are also referred to and incorporated in the specification of the present application. Clitoris including Liptocox Neoformance Tokokkusu genus such as those derived from (Cryptococcus spp), can be chosen from a flock of antigen or antigenic composition capable of eliciting an immune reacting against human pathogens.

  Furthermore, other particularly preferable antigens against tuberculosis mycobacteria are TbRa12, TbH9, TbRa35, Tb38-1, Erd14, DPV, MTI, MSL, mTTC2, and hTCC1. Proteins related to tuberculosis mycobacteria further include fusion proteins and variants thereof, and preferably at least two of the three polypeptides related to tuberculosis mycobacteria are fused to high molecular weight proteins. Preferred fusions include Ra12-TbH9-Ra35, Erd14-DPV-MTI, DPV-MTI-MSL, Erd14-DPV-MT1-MSL-mTCC2, Erd14-DPV-MTI-MSL, DPV-MTI-MSL-mTCC2, There is TbH9-DPV-MTI. The most preferred antigens for Chlamydia include, for example, high molecular weight protein (HWMP), ORF3 and putative membrane protein (Pmps). Bacterial vaccines include Streptococcus pneumoniae (eg, Streptococcus polysaccharides and their binding pairs, PsaA, PspA, streptricin, choline-binding proteins) and protein antigen pneumococci (Biochem Biophys Acta, 1989). , 67, 1007; Rubins et al., Microbial Pathogenesis, 25, 337-342) and antigens derived from their mutant detoxified derivatives Other preferred bacterial vaccines include OMP26. Non-typeable H. influenzae, high molecular weight adhesin, P5, P6, protein D, lipoprotein D, and fimbrin and finpurine derived peptides or multiple copy variants or fusion proteins thereof. Known to those skilled in the art as derivatives of hepatitis surface antigen are, among others, PreS1, PreS2 S A preferred vaccine formulation of the present invention includes the HIV-1 antigen, gp120, especially among CHO cells, According to another embodiment, the formulation of the vaccine of the present invention is as described above. GD2t as defined in.

  In addition to material delivery listed above, the apparatus and method can be used to withdraw material from a patient or to monitor the level of a patient's material. Examples of substances that can be monitored or withdrawn include blood, interstitial fluid and plasma. The withdrawn material can then be analyzed for analytes, glucose, drugs, and the like.

  The embodiments of the present invention described above include a sliding button as shown in FIGS. 11A-11C, wherein the device is first energized, then positioned on and attached to the skin surface. It is a push button type design that is activated by gradually pressing. FIG. 11A is a cross-sectional view (6-6 of FIG. 1) of the first embodiment shown in FIG. 1 before energy is applied and activated. FIG. 11B is a cross-sectional view of the first embodiment after activation and before activation, and FIG. 11C is a cross-sectional view of the first embodiment after activation.

  Specifically, as shown in FIGS. 11A and 11B, first, the user removes the device of FIG. 11A from the sterile packaging and opens the soda can or orange peel before attaching the device to the skin. In a similar motion to peeling, the handle member 260 is removed from the bottom of the device as shown in FIG. 11B to energize the system. The puller member 260 is positioned and extends to one side of the device so that it can be removed within a reasonable force that can be applied by a wide range of users and the attached retention pin 140. Produces a mechanical advantage over the removal.

  As shown in FIG. 11B, removal of the puller member 260 removes the retaining pin 140 and simultaneously removes the adhesive cover (not shown) and / or the needle cap 240 as will be described in detail below. obtain. In yet another version of this embodiment, the puller member 260 can be used for product packaging so that when the package is opened and the device is removed, the retaining pin 140, adhesive cover and / or needle cap 240 are also removed. And can be integrated.

  Prior to unpacking and using the device, the functions described above will enable the user to check the device and its components, including inspections regarding missing or damaged components, warranty periods, turbid or discolored drugs, etc. It makes it possible to check both contents. After use, the user checks the device again to ensure that all doses have been delivered. In this regard, the device may be a dosage indication such as a readable gauge area that occupies at least 20% of the surface area of the device housing and is accurate to within ± 10% of the dose shown on the label. May include a vessel.

  When the holding pin 140 is pulled a sufficient distance from the device and disengages from the spring, the finger of the disc spring 130 is released and becomes free and retracts against the container film 170 in the device. The activation button 360 and button platform 320 of the button subassembly 300 cannot be pushed until the activation button 360 is removed, so that an accidental activation or sequence of user operations is not possible. In order to prevent such mistakes, it can be either interlocked with the puller member 260 or shielded by the puller member 260 or both. Once removal of the puller member 260, retaining pin 140, adhesive cover and needle cap 240 is accomplished as shown in FIG. 11B, the device is energized and ready for positioning and activation. This energy application step releases the disc spring 130, which allows the disc spring 130 to press the flexible film 170 of the container subassembly 100 and pressurize the material communication path to the container and the septum 160, Prepare for startup.

  The next step is positioning and applying the device to the user's skin surface. Like a patch, the user presses the device firmly against the skin. The lower housing 210 includes a bottom surface that allows the adhesive layer 250 to secure the device to the user's skin. This bottom surface of the lower housing 210 may be flat, undulated, or shaped in any suitable manner and is most suitably coated prior to shipping. 250 on it. Prior to use, the user tears off the adhesive cover, such as a film covering the adhesive. Thereby, the adhesive is exposed for placement on the skin. The adhesive should preferably adhere to the bottom of the device with a peel force of at least 2 pounds (approximately 8.9 N) or less, and preferably has a pull of 1/2 pound (approximately 2.2 N) or less. Includes a cover that should be released from the adhesive with peel force. Once removed, the user can then place the device on the skin and press to ensure proper adhesion (ie, applying a vertical load of 3 pounds). In a version of the embodiment in which a removable needle cover 240 is provided, the needle cover is preferably removed from the device with a force not exceeding 2 pounds (about 8.9 N).

  When properly positioned, the device is activated by sliding the button 360 of the push button subassembly 300 and the attached button platform 320 toward the center of the device as shown in FIG. 11C. . When a force within a reasonable range is applied by the user (i.e., 2-4 pounds (about 8.9-17.8 N)), the activation button is fully depressed to allow activation. The button and button platform extend within the device and include at least one slot for holding the patient needle manifold thereon against the compressive force of one or more drive springs 310 in the unreleased position.

  When the button is pressed by the user, the first thing that happens is that the button penetrates the septum needle boot 340 and then penetrates the septum 160 and pushes the septum needle 330 so that the container and patient needle It is to create a channel between them. As described above, the “transport” position has already brought the partition boot and partition into contact. In addition, the button movement then releases the patient needle manifold 220 as described above, and the patient needle 222 is driven by the force of one or more drive springs 310 to seat in the patient's skin. It is possible to do. At this point, the button 360 and button platform 320 are locked in place and provide reliable audible and tactile feedback to the user to indicate that the infusion has begun.

  The operating sequence of the button subassembly 300 described above may be altered in other embodiments of the same or similar device. For example, in one such embodiment, when the button is pressed by the user, the first thing that happens is that the patient needle manifold 220 is released and the patient needle 222 is driven by the force of the drive spring 310 to Is allowed to sit in the skin. Further, the movement of the button then pushes the septum needle 330 through the septum needle boot 340 and the septum 160 to create a fluid path. Either method can be performed, but each failure mode may be different. For example, in an operating sequence in which flow is initiated before the patient needle manifold is released, a drenching injection typically occurs if the patient needle fails to seat properly.

  The flexible tube 350 of each embodiment connects the septum needle 330 or septum needle manifold 322, which is now in fluid communication with the container, to the patient needle manifold 220, which is now in fluid communication with the user, for patient use. It is flexible enough to allow the needle manifold to move independently from any of the other device components. In addition, the tube 350 also serves as a required flow restriction member because it has a tortuous path established by the path of the patient needle manifold described above.

  Once activated, the user can either leave the device in place or wear the device to completely deliver the contents of the device for any time, eg, 10 minutes to 72 hours. wear. The user then removes and discards the device without damaging the underlying tissue. However, as soon as it is intentionally or accidentally removed, one or more safety mechanisms are deployed as described in detail below to shield the exposed needle caused by activation. However, the safety mechanism may be configured so that it does not deploy if the buttons and button carriage are not pushed and the patient needle does not protrude.

(Safety mechanism)
To avoid inadvertent or accidental needle sticks and intentional reuse of the device, and to shield exposed needles, a locking needle safety mechanism is provided as soon as the device is removed from the skin surface. It starts automatically.

  One version of an embodiment of the safety mechanism is provided with a patient needle cover that rotates in response to an external action as shown in FIGS. 17A and 17B. FIG. 17A is a perspective view of the safety shield mechanism of the embodiment of the present invention before energy application and activation, and FIG. 17B is a perspective view of the safety shield mechanism after energy application and activation.

  The rotating shield 230 may be actuated by a pre-loaded torsion spring 232, shown in FIG. 10B, which remains mounted in a “up” position until the pushbutton subassembly button is pressed. It is up to. The shield 230 then becomes free and rotates. However, the presence of the user's skin against the adhesive coated surface of the device prevents rotation to the fully deployed position. When the device is no longer against the user's skin, such as when the device is removed or free, the shield 230 is no longer disturbed by the skin surface and rotates approximately 180 degrees, Then it is fixed in place and completely covers the patient needle 222 to prevent injury from needle stick.

  In another version of the safety mechanism embodiment, as shown in FIGS. 18A and 18B, a safety housing is provided that partially provides a flat surface portion 252 that is in contact with the patient's skin. FIG. 18A is a perspective view of the safety shield mechanism of the embodiment of the present invention before energy application and activation, and FIG. 18B is a perspective view of the safety shield mechanism after energy application and activation.

  The surface 252 is also exposed when the device is removed from the skin by the patient, the adhesive deploys (ie, retracts or pulls out) the safety housing 254 from the interior of the device, thereby removing it from the patient. It includes an adhesive disposed thereon to act to shield the patient needle 222 that would be intended. The protruding safety housing 254 is then locked in place as shown in FIG. 18B to prevent accidental injury or patient needle exposure.

  Yet another version of the safety mechanism embodiment includes a flexible patient needle cap 240 that helps protect the patient needle and provides a sterility barrier. The needle cap protects the patient needle during device manufacture, helps protect the user prior to use, and may provide a sterility barrier at any point prior to removal. Needle cap 240 may be attached by a press fit with patient needle manifold 220 and further provides a flexible member 242 that may be used to secure the cap to puller member 260. As noted above, removal of the retaining pin 140 can also help to remove the needle cap 240, and the cap and / or puller member can further provide an interlocking mechanism with the buttons of the push button subassembly.

  Still another effective safety device mechanism may be provided separately from the above-described mechanisms or may be provided in combination. The mechanism allows the user to position or activate the shield as needed. For example, the safety device is manually turned or moved between the exposed position and the shielded position, and after use, the user actively shields the patient's needle, causing accidental injury or exposure to the needle. One or more levers or a rotation mechanism as described above may be included.

  In each of the safety device versions described above, the force to deploy the described safety mechanism applies a force of 3 pounds (approximately 13.3 N) or more that removes the device from the skin surface and typically overcomes the fixation mechanism. Less than the peel force that needs to be done. For example, the safety mechanisms each provide protection from a 2 pound (about 8.9 N) fingertip load on the needle tip. Further details of the protruding shield and use are further described in the above referenced US patent applications 60 / 397,038 and 60 / 407,284. The entire contents of each are incorporated herein by reference. Further details of the rotating shield and use are further described in the previously referenced US patent applications 60 / 447,359, 60 / 450,680 and 60 / 450,681. The entire contents of each are incorporated herein by reference.

  In addition to the performance advantages described above, another advantage of the embodiment of FIG. 1 described above is the ability to create two or more different self-contained subassemblies that allow for assembly flexibility. Each sub-assembly is self-contained, stable and provides the ability to separate the container assembly from the remaining components, allowing independent container filling and inspection, while the remaining components To prevent unnecessary handling. Furthermore, expensive container contents can be excluded, even if any supplemental components are removed. Also, the container does not contain any unnecessary parts. As a result, the filling operation results in a low particulate load. Also, all stored energy components are in the body subassembly so that they cannot be inadvertently deployed during container filling. In particular, the spring is not contained within the container, thus preventing the opportunity for undesired spring release during filling. As noted above, the minimal foreign components of the container reduce the particulate loading and only include the necessary components such as containers, lids, septa and stoppers. There are no dangling parts. Also, the remaining parts for the remaining subassemblies typically require a drop-down assembly step.

  A further advantage of the embodiment of FIG. 1 described above includes a location for the patient needle near the center of the device bottom area. Such an arrangement reduces the effects of needle displacement due to device movements such as “rocking”. The patient needle manifold has a low mass, in part due to a separate manifold for the septum, and is thus configured to provide a faster speed to the patient needle manifold during activation. The patient needle manifold is provided with a direct drive member that is independent of the patient needle so that the drive spring is positioned directly above the patient manifold and serves exclusively to drive the patient needle manifold. Septum penetration and boot collapse forces have no effect on the movement of the patient needle manifold. In addition, there are chambers that contain a larger needle space, and a smaller starting force is sufficient. However, inadvertent activation due to such a small force is prevented by many activation lockout members.

  Just as a well-spaced chamber is provided in older urethane septum needle boots, a well-spaced chamber restricts flow, such as a flexible tube, ie a capillary tube. Any number of flow restriction mechanisms can be used. This mechanism can be provided at the same time as keeping the bottom area of the device small. In addition, a container can be placed on top of the device that allows a complete and unobtrusive view of the drug container through the transparent component and can allow the user or manufacturer to view the contents of the container.

(Second embodiment)
A second embodiment of the device shown in FIGS. 19A and 19B is a push button design 400 where the activation and energization of the device is accomplished in a single multifunction / step process. 19A is an exploded perspective view of a second embodiment of a patch injector or infuser system using a side push button, and FIG. 19B is a cross-section of the patient needle / septum needle manifold system of the second embodiment. 19C is a cross-sectional view of the second embodiment shown in FIG. 19A before energy application and activation, and FIG. 19D is a cross-section of the second embodiment shown in FIG. 19A after energy application and activation. FIG.

19A-19D includes a top housing 410 and a rigid bottom 415, a spring lock pin 420, a push button 430, a manifold 440, a disc spring 460 and a container lid 480. The manifold 440 further includes one or more patient needles 442 and at least one septum needle 444 that pierces the septum 446 .

  19A and 19C, the cams 431 and 432 on the inner part of the button push the spring lock pin 420 and release the spring 460, thereby pressing the sliding button 430 to pressurize the container system. Is activated and given energy. As button 430 continues to travel along its travel as shown in FIG. 19D, the button will move both patient needle 442 and septum needle 444 (positioned in the same direction) as shown in FIG. 19B. Engages a number of cam mechanisms that lower the needle assembly and manifold 440 toward the patient's skin.

  Specifically, in addition to energizing the container of the device by releasing the constant force spring 460, the cam surface inside the button 430 engages the engagement surface of the needle manifold assembly 440, which To drive the manifold assembly toward the opening in the lower surface of the apparatus. The continuous movement of the button pushes the needle 442 protruding from the needle manifold 440 into the user's skin, bringing the fluid access nail, or septum needle 444, into the container, thereby once the needle is positioned. Then, the fluid starts to flow from the container to the user's skin. Since both needles 442 and 444 are relative to the skin surface, the respective skin contact mechanism and air bag piercing mechanism are guaranteed. As will be appreciated by those skilled in the art, the cam surface of the button assembly may be configured to change speed or reposition the series of events just described. Further details of the push button design in which device activation and energy application are accomplished in a single multifunction / step process are further described in previously referenced US patent application Ser. No. 60 / 397,038. The entire contents of which are hereby incorporated by reference.

(Third embodiment)
A third embodiment of the device, shown in FIGS. 20A-20C, is a manifold in which the bladder itself moves toward the patient's skin and has both a patient needle and a septum needle (positioned in opposite directions). A push button design 500 that pushes the patient needle into the patient's skin and pushes the septum needle into the septum. FIG. 20A is an exploded perspective view of a third embodiment of a patch injector or infuser system using a side push button, and FIG. 20B is a cross-sectional view of the third embodiment prior to energy application and activation. FIG. 20C is a cross-sectional view of the third embodiment showing after energy application and activation.

  20A-20C includes a pin puller member 505, a top housing 510, a leaf spring 520, a container top 525, a disc spring 530, a container lid 535, a container bottom 540, a septum 545, a manifold system 550, a push button 555, a bottom. A housing 560, a safety clip 565 and a needle clip 570 are included. In a manner similar to the first embodiment described above, the user imparts energy to the device of the third embodiment shown in FIG. 20B by removing the pin puller member 505 from the device. Once this is done, the device is now free of disc springs 530, pushing the container down and pressurizing the fluid in the container system, as shown in FIG. 20C and described in detail below. Energy is applied as the container is pushed downward for engagement.

In the third embodiment shown in FIG. 20 , the device pushes the button 555 until the button no longer holds the container bottom 540 in place relative to the top housing 510 and resists the force of the leaf spring 520. It is activated by sliding towards the center of the device. As part of the container system, the container top 525 is preferably rigid, the spring is loaded, and the container lid 535 is sealingly connected to the container bottom 540 so that the container system is now a single unit. Moves downward as a unit toward the patient's skin. At this time, the needle manifold reaches the bottom of the bottom housing 560 of the device. A septum 545 can also be disposed on the container bottom 540. The needle containment manifold 550 is attached to a rigid bladder assembly and the manifold 550 also moves toward the patient's skin until the patient needle pierces the skin. The container assembly continues to move slightly downward, causing a fluid access nail, or septum needle, to pass through the septum 545, thereby initiating fluid flow from the container through the patient needle or needles. .

  One particular feature of the third embodiment is that the septum needle accesses the container from below as the container moves downward. This allows the device to shrink in the height direction and, once activated, allows for a low profile. Furthermore, since the penetration of the septum needle is in the opposite direction as the penetration of the patient needle, there is no need for additional height in the device and no need for additional height of the internal space or the entire device. Allows the needle to be maintained in a sterile state. For further details of the push button design in which the bladder itself moves toward the patient's skin and contacts a manifold having both a patient needle and a septum needle, see previously referenced US patent application Ser. No. 60/397, This is further described in No. 038. The entire contents of which are hereby incorporated by reference.

(Fourth embodiment)
A fourth embodiment of the device shown in FIGS. 21A-21C is that the push button is placed on the top outer surface of the device and the user applies energy by depressing the button to its lowest position and the fluid flow Push button design to launch FIG. 21A is an exploded perspective view of a fourth embodiment of a patch injector or infuser system using a top push button, and FIG. 21B is a view of the fourth embodiment shown in FIG. 21A prior to energization and activation. FIG. 21C is a partial cross-sectional view of the fourth embodiment shown in FIG. 21A after energy application and activation.

  The apparatus of FIG. 21A includes a top push button 602, an upper housing 605, a leaf spring 610, a manifold assembly 615, a pull pin 620, a release guide member 630, a retainer 635, a disc spring 640 and a container 645. Similar to the previous embodiment described above, adhesives 655 and 660 are exposed on the bottom surface of the device, and the user presses the device against the skin in the desired area of the body and attaches the device securely. Once the device is in place, the user depresses the button 602 located at the top of this embodiment. Depressing the push button 602 forces the manifold assembly 615 located directly below the button to move downward. The manifold assembly also includes an inclined surface that engages the protrusion of the release guide member 630. As the manifold assembly 615 moves downward, the release guide member 630 moves its attachment along the groove of the retainer 635 or the leaf spring 610 in the guide toward the pull pin 620 to the constant force spring 640. . The pull pin 620 is configured and shaped to fit within the retainer 635 and is preferably retained within the retainer by the retainer pin 625. This shape allows the pull pin 620 to rotate freely around the holding pin 625. On the other hand, the release guide member 630 is forcibly moved along the guide in the cage 635. The lower surface of the release guide member 630 has a grooved surface that slides along the grooved surface of the pull pin 620, depresses one end of the leaf spring 610 and the pull pin, Rotate around the holding pin 625 and lift the other end of the tension pin attached to the constant force spring 640. This rotation and lifting overcomes the holding force of the pull pin, which releases the constant force spring, thereby imparting energy to the container 645.

  A manifold assembly 615 comprising a septum piercing needle or nail and a skin penetrating needle or needles is also fully implanted at the desired depth of the skin at the same time as the downward movement of the push button occurs. Pushed down until. The bulkhead nail then accesses the fluid in the container and allows the fluid in the container to flow before and after the container is energized depending on the configuration. As with the embodiments described above, each configuration can be modified to affect the timing and sequence of events described above. For more details on the push button design where the push button is located on the outer surface of the top of the device and the user depresses the button to its lowest position to energize and activate fluid flow, see above Further U.S. Patent Application No. 60 / 407,284. The entire contents of which are hereby incorporated by reference.

(test results)
Various results and comparisons between preferred device embodiments and other methods and devices are shown in FIGS. The graph of FIG. 22 shows the flow uniformity over a long delivery time in vitro to establish the measured flow used in subsequent trials with diabetic pigs. This is further illustrated in FIG. 26 showing pressure versus delivery volume data in accordance with an embodiment of the present invention. The use of a Belleville spring that applies pressure to the flexible container results in a substantially constant delivery over a 25 hour infusion period using the embodiment of FIG. 1 described above.

  The graph in FIG. 24 shows the mean blood insulin concentration (pharmacokinetic response) measured in several animals over the insulin delivery period. This is initially very low due to the diabetic state of the animal, and then increases to a much higher concentration during infusion. At the end of the infusion, the insulin concentration returns to a low baseline concentration. A small peak occurs at the mean baseline insulin concentration of negative control animals that have never received insulin. These peaks reflect minimal endogenous insulin secretion by the animals corresponding to feeding times -1, 7, 14, 21 and 28 hours. The infusion data illustrated in FIG. 22 shows that the results according to the above-described embodiments of the present invention are as desirable as those obtained using a standard insulin pump. Further details of the pharmacokinetic overview can be found in US Patent Application Publication No. 2002/2002, filed June 29, 2001, whose title is “Method of Changing Drug Pharmacokinetics Based on Medical Delivery Platform”. No. 0095134. The entire contents of which are hereby incorporated by reference.

  The graph of FIG. 23 shows the mean blood glucose concentration (pharmacokinetic response) measured in several animals over an insulin delivery period according to an embodiment of the present invention. Blood glucose concentration is affected by additional glucose given to animals to prevent feeding and hypoglycemic damage. As a result, there are periodic peaks in blood concentration corresponding to supply times -1, 7, 14, 21 and 28 hours. The blood glucose concentration of both the syringe and insulin pump that handles animals drops significantly within the first 5 hours of insulin delivery. Blood glucose levels remain generally below the response of negative control diabetic animals that have not received any insulin for the remainder of the experimental period. The effect of blood glucose obtained with an injector as shown in FIG. 23 is approximately equal to the result obtained with a standard insulin pump. 22 and 23, the performance of the pump and microinjector is quite similar, resulting in a very similar physiological response.

  The graph of FIG. 25 shows blood insulin measured in animals receiving insulin from a syringe designed to deliver a larger dose of insulin as a “metered bolus” over a period of 2-3 minutes. Concentration (pharmacokinetic response) is shown. In the embodiment of FIG. 1, the injector achieves approximately the same result as obtained from subcutaneous injection using a standard syringe.

  Although only a few exemplary embodiments of the present invention have been described in detail above, those skilled in the art will recognize that many changes in the exemplary embodiments may be made without significantly departing from the novel teachings and advantages of the present invention. You will easily understand that is possible. Accordingly, all such modifications are intended to be included within the scope of this invention as set forth in the following claims.

1 is a top perspective view of a first embodiment of a patch injector or injector system using a side push button prior to energization and activation. FIG. 1 is a bottom perspective view of a first embodiment of a patch injector or injector system using a side push button. FIG. 1 is a top view of a first embodiment of a patch injector or injector system that uses a side push button. FIG. 1 is a side view of a first embodiment of a patch injector or injector system that uses a side push button. FIG. 1 is a bottom view of a first embodiment of a patch syringe or infuser system using a side push button. FIG. FIG. 6 is a cross-sectional view (6-6 of FIG. 1) of a first embodiment of a patch injector or infuser system using a side push button. FIG. 6 is a cross-sectional view (6-6 in FIG. 1) of the first embodiment of the patch-like syringe or infuser system using a side push button, as seen from a first perspective angle. FIG. 6 is a cross-sectional view (6-6 in FIG. 1) of the first embodiment of the patch injector or infuser system using the side push button, as viewed from a second perspective angle. FIG. 6 is a cross-sectional view (6-6 in FIG. 1) of the first embodiment of the patch injector or infuser system using the side push button, as viewed from a third perspective angle. FIG. 2 is an exploded view of the container subassembly of the first embodiment shown in FIG. 1. FIG. 2 is an exploded view of the housing subassembly of the first embodiment shown in FIG. 1. FIG. 2 is an exploded view of the push button subassembly of the first embodiment shown in FIG. 1. FIG. 6 is a cross-sectional view (6-6 in FIG. 1) of the first embodiment shown in FIG. 1 before energy application and activation. FIG. 6 is a cross-sectional view (6-6 in FIG. 1) of the first embodiment shown in FIG. 1 after energization and before activation. It is sectional drawing (6-6 of FIG. 1) of the 1st embodiment shown by FIG. 1 after starting. FIG. 10B is a partial cross-sectional view of the fluid passage and the container subassembly of FIG. 10A. 6 is a graph illustrating an example of insulin stability data for a container subassembly according to an embodiment of the present invention. It is a graph which shows the example of the disc spring calculation data concerning the embodiment of the present invention. 1 is a perspective view of a preferred embodiment of a patient contact manifold structure of a patient needle manifold with respect to a patient needle manifold. FIG. FIG. 15B is a perspective view of another patient contact surface structure for the patient needle manifold of FIG. 15A. FIG. 11 is a top perspective view of another embodiment of the subassembly of FIGS. 10A-10C partially assembled. FIG. 16B is a cross-sectional view of the subassembly shown in FIG. 16A prior to energy application and activation. FIG. 16B is a cross-sectional view of the subassembly shown in FIG. 16A after energy application and activation. It is a perspective view of the rotating safety shield mechanism of the embodiment of the present invention before energization and starting. FIG. 6 is a perspective view of a rotating safety shield mechanism of an embodiment of the present invention after energization, activation and release from the user's skin surface. It is a perspective view of the protrusion shielding body mechanism of the embodiment of the present invention before energization and starting. FIG. 5 is a perspective view of a protruding safety shield mechanism of an embodiment of the present invention after energization, activation and release from a user's skin surface. FIG. 6 is an exploded perspective view of a second embodiment of a patch injector or infuser system using a side push button. FIG. 19B is a cross-sectional view of the second embodiment of the patient needle / septum needle manifold system shown in FIG. 19A. FIG. 19B is a cross-sectional view of the second embodiment shown in FIG. 19A before energy application and activation. FIG. 19B is a cross-sectional view of the second embodiment shown in FIG. 19A after energy application and activation. FIG. 6 is an exploded perspective view of a third embodiment of a patch injector or infuser system using a side push button. FIG. 20B is a cross-sectional view of the third embodiment shown in FIG. 20A before energy application and activation. FIG. 20B is a cross-sectional view of the third embodiment shown in FIG. 20A after energy application and activation. FIG. 3 is an exploded perspective view of a patch injector or infuser system using a side push button. FIG. 21B is a partial cross-sectional view of the fourth embodiment shown in FIG. 21A before energy application and activation. FIG. 21B is a partial cross-sectional view of the fourth embodiment shown in FIG. 21A after energy application and activation. FIG. 3 is an example of infusion data in a test tube showing a flow rate over 38 hours. FIG. It is a graph which shows an example of the blood glucose level data of blood. It is a graph which shows an example of the insulin value data of blood. It is a graph which shows an example of insulin response data. It is a graph which shows an example of pressure versus delivery volume data.

Claims (43)

A fluid container containing fluid to be infused into a patient having opposing flexible and rigid walls defining a fluid chamber therebetween;
At least one patient needle in fluid communication with the container;
A fluid flow path providing the fluid communication between the container and the patient needle when a fluid flow path is completed;
A push button actuator for starting the operation of the patch injection device by completing the fluid flow path;
A protector or connector that prevents operation of the pushbutton actuator until a previous operation is performed that includes at least removing a protective cap from the patient needle ;
An energy storage device that applies pressure to the flexible wall of the container to cause fluid to flow from the container to the patient needle;
A patch-like injection device comprising:   2. The patch injection device according to claim 1, wherein the energy storage device includes a spring.   The patch-like injection device according to claim 2, wherein the spring includes a disc spring.   2. The patch injection device of claim 1, wherein the container is at least partially transparent to allow its contents to be visually inspected.   The patch injection device according to claim 1, wherein the flexible wall is made of a plastic film.   The plastic film is selected from the group consisting of a first layer of linear low density polyethylene, a second layer of low density polyethylene, a third layer of aluminum, a fourth layer of low density polyethylene, and nylon and polyester. 6. The patch injection device according to claim 5, comprising 5 layers.   The patch injection device according to claim 1, wherein the hard wall includes a cyclic olefin copolymer (COC) layer.   The patch of claim 1, further comprising actuating means for initiating the energy storage means to apply the pressure to the flexible wall of the container when the infusion device is in use. Injection device.   9. A patch according to claim 8, wherein the energy storage device comprises a disc spring having a central opening, and the actuating means comprises a retainer engagable with and removable from the opening. Injection device.   The patch-type injection device according to claim 9, wherein the retainer includes a pin. The disc spring has a central opening for applying pressure to the flexible wall to cause fluid to flow from the container to the patient needle;
10. The patch injection device according to claim 9, wherein the retainer starts the disc spring to apply the pressure when the injection device is put into operation.   The patch injection device according to claim 11, wherein the retainer includes a pin.   12. The patch injection device of claim 11, wherein removal of the retainer from the opening provides at least one audible indicator and tactile indicator to a user of the injection device.   12. The patch injection device of claim 11, wherein removal of the retainer from the opening occurs automatically when a user performs another operation of the injection device.   The patch-like injection device according to claim 14, wherein the operation includes operating the push button actuator.   The patch-like injection device according to claim 14, wherein the operation includes removing the protective body or the coupling body.   The fluid flow path pierces a first pierceable septum that blocks fluid flow from the container, and the first pierceable septum, passing the fluid through the flow path to the patient needle. The patch injection device according to claim 1, further comprising a septum needle different from the patient needle to be guided.   The patch fluid injection device according to claim 17, wherein the fluid flow path further comprises a single flexible tube interposed between the septum needle and the patient needle.   19. The patch injection device of claim 18, further comprising a patient needle manifold for carrying the patient needle, wherein one end of the one flexible tube is connected to the manifold.   18. The patch injection device according to claim 17, wherein the fluid flow path includes a flow restrictor that controls a fluid injection amount to a patient.   The patch injection device according to claim 17, wherein the patient needle has a gauge smaller than the septum needle.   The patch injection device of claim 21, wherein the patient needle is 31 gauge or smaller.   18. The patch injection device of claim 17, wherein the fluid flow path includes a filling port that allows the container to be filled with a fluid.   The filling port includes a second pierceable septum, and the first pierceable septum and the second pierceable septum are spaced apart from each other with a chamber therebetween. 24. The patch injection device according to claim 23, wherein the chamber is defined and the chamber forms part of the fluid flow path. A manifold in fluid communication with the patient needle that supports the patient needle and directs fluid from a manifold inlet to the patient needle;
The manifold comprises a hard lower portion defining an upwardly facing internal cavity open at the top of the hard lower portion, the lower portion having the patient needle protruding from a lower surface thereof, the manifold Further comprising a flexible film adhered to the top of the rigid lower portion that closes the cavity and thereby defines an interior chamber in the manifold that is in fluid communication with the manifold inlet. The patch injection device according to claim 1.   26. The patch injection device according to claim 25, wherein the hard lower portion is made of an acrylic polymer.   26. The patch injection device according to claim 25, wherein the flexible film is made of a metal-deposited plastic laminate. 26. The patch injection device of claim 25, wherein the flexible film is adhered to the top of the hard lower portion by heat sealing .   26. The patch injection device of claim 25, wherein the cavity is configured to minimize the volume of fluid within the manifold. 26. The patch injection device of claim 25, wherein a plurality of patient needles are provided and the manifold includes a fluid pathway connecting the cavity to the patient needle .   31. The patch injection device according to claim 30, wherein the patient needles are arranged in a linear pattern. A housing;
A rotatable safety shield housed by the housing that covers the patient needle after use of the infusion device;
Further comprising
The fluid container is provided in the housing;
The patch-like infusion device according to claim 1, wherein at least one of the patient needles is received by the housing.   The patch injection device of claim 32, wherein the safety shield is rotatable about an axis substantially parallel to the patient contacting surface of the housing.   The safety shield is rotatable about the axis between a retracted position and a protruding position in the housing, and the safety shield protrudes below the patient contact surface and covers the patient needle. 34. The patch injection device according to claim 33.   33. The patch injection device according to claim 32, further comprising a spring that rotates the safety shield to the protruding position after use of the injection device. The at least one patient needle is projectable from the housing;
33. The fluid flow path of claim 32, comprising a fill port accessible from outside the housing that allows the container to be filled after the infusion device is fully assembled. The patch injection device as described.   37. The patch injection device according to claim 36, wherein the filling port includes a pierceable partition wall.   The patch-like infusion device according to claim 1, wherein the preceding operation includes pressurizing the fluid container. The patch injection device according to claim 1, wherein the patient needle moves from the shielded position to the injection position in response to an operation of the push button actuator. A housing;
A patient needle manifold that defines a common chamber in fluid communication with the fluid container that is in the housing and receives the fluid therefrom;
A plurality of patient needles that receive the fluid from the common chamber and can be accommodated by the manifold;
Further comprising
The fluid container is provided in the housing;
The patient needle manifold is in a first position within the housing, where the patient needle is shielded within the housing, and the patient needle for injection into a patient's skin. 2. The patch-like injection device according to claim 1, wherein the injection device is movable between a second position protruding from the housing. 41. The patch injection device of claim 40, wherein the patient needle projects through an opening in the bottom surface of the housing when the manifold is in the second position. 41. The patch injection device of claim 40, wherein each of the patient needles is 31 gauge or smaller and has an exposed length of 4 mm or less. 41. The patch injection device of claim 40, further comprising a push button actuator that moves the patient needle manifold from the first position to the second position.

Images